Trisomy 21, commonly referred to as Down Syndrome, is the most frequent fetal chromosomal abnormality, affecting approximately 1 in 800 infants. It is associated with mental retardation, structural defects involving the heart and/or the digestive tract, increased incidence of respiratory infections, high incidence of fluctuating hearing loss, and thryoid and cervical spine abnormalities.
Generally, Down Syndrome can only be diagnosed by invasive procedures such as amniocentesis, which involves sampling the amniotic fluid, and chorionic villus sampling (CVS), which involves sampling the chorionic villi from the placenta. These invasive diagnostic procedures, however, involve risk to the mother and the fetus and therefore are not routinely performed during all pregnancies. Instead, one or more screening methods may be utilized to determine whether the risk of Down Syndrome to the pregnancy warrants the risk of undergoing an invasive and risky diagnostic procedure. Such Down Syndrome screening methods typically include measuring levels of screening markers such as free β human gonadotrophin (hCG), pregnancy associated during the first trimester of pregnancy. Although screening methods using such markers can detect 85-90% of Down Syndrome cases, they do so at a 5% false positive rate.
Currently research, therefore, is now focused on modifying the 85-90% screening protocol to lower the 5% false positive rate while maintaining the 85-90% detection efficiency. For example, one approach described in Wald N J, Watt H C, Hackshaw, A K. N. Engl J Med, 341(7):461-7 (Aug. 12, 1999) suggests measuring levels of screening markers during two stages of pregnancy, i.e. during the first and second trimester to determine a patient's risk of having a fetus with Down Syndrome. Although such an approach may reduce the false positive rates of detection, it presents the disadvantage of not providing a result until later in pregnancy. A better approach would be using additional screening markers during the first trimester to maintain the advantages of early detection. Two additional markers that have been suggested are blood flow in the ductus venous and nasal bone identification. Measurement of both of these markers, however, is quite difficult to perform and requires a significant amount of training even for experienced sonographers. In addition, there is some concern about the safety of using color Doppler ultrasound during pregnancy to measure the ductus venosus blood flow.
Accordingly, there is a need for additional methods of screening for fetal abnormalities, such as Down Syndrome, that carry a low false positive rate and that can easily and safely be performed early in pregnancy.